Androstanes are steroids having a skeleton of the formula hexadecahydro-10,13-dimethyl-1H-cyclopenta[a]-phenanthrene. The compounds with only a 13-methyl group are named 19-norandrostanes. Androstanes with an ethyl side-chain at the 17-position are named pregnanes. For reasons of simplicity only the term androstane is used in this description. The term androstane may, however, also be read as 19-norandrostane, pregnane, or 19-norpregnane. In the experimental section the usual chemical names are used.
Derivatives of androstane having intravenous anaesthetic activity are known in the art. They have less side effects when compared with other steroidal anaesthetics. These steroids may carry substituents at several positions (see for example British patents 1,376,892, 1,380,248, 1,430,932, 1,570,394, 1,377,608, and 1,581,234; and U.S. Pat. No. 3,983,111). A well-known example is alfaxalone as disclosed in German patent 2,030,402.
It has been found these steroids when substituted by various groups may have advantageous properties, but substitution may also lead to decrease of anaesthetic activity.
It is of particular advantage to have water soluble anaesthetic compounds, since such compounds can advantageously be used for intravenous anaesthesia. Anaesthetic androstane derivatives having groups which improve the water solubility at various positions of the steroid skeleton, are known. Introduction of such groups does not always lead to increase of activity or stability. In the search for water-soluble anaesthetic androstane derivatives having intravenous activity, 2.beta.-amino-derivatives, and particularly 2.beta.-morpholino derivatives were claimed to be favourable. Androstane derivatives having a morpholino group attached at the 2.beta.-, 11.alpha.- or 21-positions of the steroid are disclosed as compounds with anaesthetic activity, for example in British patents 1,377,608 and 1,581,234, and in U.S. Pat. No. 3,983,111. However, the 2.beta.-morpholino derivative of alfaxalone is significantly less active than alfaxalone itself.